Chapter 21: Immunoprophylaxis and Immunotherapy

I. Immunoprophylaxis

II. Immunotherapy

I. ImmunoprophylaxisConception

1. The way of acquired specific immunization

2. The classification and characteristics of

Artificial immunization

3. Biological product and their application

1. The way of acquired specific immunization

Natural immunization: heredity, non-specific

Acquired immunization: acquired, specific

Active immunization: natural, artificial

Passive immunization: natural, artificial

Immunity can be acquired through active and passive immunization

Type acquired through

Active immunization: Natural infection or inapparent infection Artificial infection: vaccine, toxoid, attenuated organisms inactivated organisms purified microbioal macromoleculesPassive immunization: Natural maternal antibody Artificial immune serum

I. ImmunoprophylaxisConception

1. The way of acquired specific immunization

2. The classification and characteristics of

Artificial immunization

3. Biological product and their application

2. The classification and characteristics of Artificial immunization

Artificial active immunization:

Artificial passive immunization:

Comparison:

Artificial active immunization Conception:

Features: 1. The production of the effect:

slow ( induction phase:1-4weeks )

2. The persistent time of immunity:

long (months-years)

3. The application: specific prophylaxis

4. The agents: Ag: vaccine, toxids

Artificial passive immunization Conception:

Features: 1. The production of the effect: fast

2. The persistent time of immunity: short (2-3weeks)

3. The application: treatment and urgent prophylaxis

4. The agents: Ab: antitoxin

antiserum

human gammaglobulin

synthetic peptides

anti-idiotype antibodies

Artificial active Artificial passive immunization immunization

Injecting agents: Ag (vaccines, toxids) Ab (antitoxin, antiserum) Producting time: slow (induction phase:1-4W) at oncePersistenting time: long (months or years) slow (2weeks or months)The main application: specific prophylaxis urgent prophylaxis or (infectious diseases) treatment

I. ImmunoprophylaxisConception

1. The way of acquired specific immunization

2. The classification and characteristics of

Artificial immunization

3. Biological product and their application

3. Biological product and their application

Biological producta. Vaccine: Live vaccine (attenuated vaccine) Killed vaccine Comparison*:b. Toxoid: TAT, DATc. New vaccine: Live vaccine Chemical vaccine or subunit vaccine Compound vaccine Genetic engineering vaccine Anti-idiotype vaccine

死疫苗和活疫苗的比较

活疫苗 死疫苗

接种方式： 模拟自然感染途径 皮下注射 （皮内，划痕法）接种剂量： 较小 较大接种次数： 多数只需一次 两次或多次 （体内有一定繁殖） （体内不繁殖）副作用： 反应较小 反应较大 （发热、全身或局部反应）免疫效果： 较好，持续 3-5 年或更长 较差，持续数月 -1 年疫苗保存： 易失效，冻干 4C 保存 较易保存，较稳定

Recombinant vaccine

DNA from pathogen

Plasmid

Vaccinia promoter

Ligation

Plasmid

Recombinantplasmid

Vaccinia virus

transfection infection

Animal-cell culture

Recombinant vaccinia

Anti-idiotype antibodies as vaccine

antibodyantigen

Antigen may be protein,carbohydrate,etc.

Antigenicdeterminant

Miceimmunized idiotype1

First antibody selectedfor high affinity forimmunizing antigen,made monoclonal

Anti-idiotype antibodiesRaised against idiotype 1

Second antibodiesscreened for similarityto original antigen

Anti-idiotype 1

Anti-idiotype 1

like antigen unlike antigen

vaccine

II. ImmunotherapyConception

1. Immunopotentiator and indication

2. Immunosuppressant and indication

3. Immunomodulator and the use of them

1. Immunopotentiator and indication

a. Immunopotentiator:

Chemical agents:

levomisole, cimetidine,isoprinosine(ISO)

Microbiological agents: BCG, vp

Proteins of immune system: Ig,iRNA

b. Indication:

e.g. Tumor, Immunodeficiency, Infectional diseases

2. Immunosuppressant and indication

a. Immunosuppressant*: Chemical agents: Cyclophosphamide, Cy Azathioprine, Aza Hormone: steroids Microbiological agents: CyclosporineA(CsA), Tacrolimus, FK-506 b. Indication: Organ transplantation Hypersensitivity diseases Autoimmune diseases Infectious diseases

Immunosuppression with Drugs

Steroids

APC

Graft cells

MHC-ITCR-CD3

CD8

Tc

Tc

Th proliferation

Cyclosporin Azathioprine

M

TCR-CD3

CD4

MHC-II

Tc

IL-2R

IFN IL-2

inactivation

抑制免疫应答：抑制免疫应答： Hypersensitivity DiseaseHypersensitivity Disease Autoimmunity DiseaseAutoimmunity Disease Graft rejection responsesGraft rejection responses

Anti-B7AbCTLA4 IgAnti-CD28

阻断 co-stimulatory signals

THAPC MHC TCR

Ag

CD28

B7

3.Immunomodulator and the use of them

a. Biological response modifier, BRM

b.Classification and function of BRM

b.Classification and function of BRM 1. Immunoreconstitution: hemopoietic stem cell and thymus 2. Monoclonal antibodies (McAb) and targeted drug McAb: Anti-CD3, Anti-CD4, Anti-CD8 Targeted drug*: Immunotoxin, IT Immunoconjugate, Radioimmunoconjugate 3. Cytokines and actived immune cells Cytokines*: Ils, IFN, TNF, CSF, TGF and Small molecular polypeptides. Immune cells: LAK, TIL 4. Tumor vaccine 5. Gene therapy*: CK gene therapy

Tumor

McAb-toxin

McAb-enzyme

McAb-medicine

McAb-isotope

Cytokine therapy for tumorsCytokine tumor type and results Cytokine effects and possible anti-tumor mechanisms Prolonged remissions of possible cytostatic

hairy-cell leukemia effect on tumorweak effects on some increased expression of carcinoma MHC class I, cytostasis

remission of peritoneal increased MHC class I and II carcinoma of the ovary macrophage activation

Tc activation, cytostasis

IFN

IFN

IL-2Remission in renal cancer T-cell activation and and melanoma proliferation NK-cell activation

TNF ? Increased tumor cell adhensioncan reduce macrophage and lymphocyte malignant ascites activation

Enhancing immune responseEnhancing immune response ：： Tumor immunity treatmentTumor immunity treatment

B7

TransfectionB7gene

CTLMHC TCR

Ag

CD28

Tumor cellsignal1

signal2

CTLMHC TCR

Ag

CD28

Tumor cellsignal1

signal2

CTLactivatedKiller tumor cell

CTLactivatedKiller tumor cell